tbuckley/cabot-search huggingface dataset:
Clinicopathologic Analysis of Breast Cancers with <i>PIK3CA</i> Mutations in Japanese Women
Authors: Naomi Maruyama, Yasuo Miyoshi, Tetsuya Taguchi, Yasuhiro Tamaki, Morito Monden, Shinzaburo Noguchi
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Somatic mutations of PIK3CA, which encodes the p110α catalytic subunit of phosphatidylinositol 3-kinase, have recently been shown to play an important role in the pathogenesis and progression of human breast cancers. In this study, the frequency of PIK3CA mutations and their relationship with clinicopathologic and biological variables were investigated in Japanese breast cancers. Experimental Design: Mutational analysis of PIK3CA was done in 188 primary breast cancers of Japanese women. Relationship of these mutations with various clinicopathologic variables [histologic type, tumor size, histologic grade, lymph node status, estrogen receptor (ER)-α and progesterone receptor status, and prognosis], biological variables [phospho-AKT (pAKT) and HER2 expression determined by immunohistochemistry], and p53 mutation status was studied. Results: Missense mutations of PIK3CA were found in 44 of 158 invasive ductal carcinomas, 4 of 10 invasive lobular carcinomas, 1 of 4 mucinous carcinomas, 2 of 2 squamous carcinomas, and 2 of 2 apocrine carcinomas, but no mutation was found in 12 noninvasive ductal carcinomas. PIK3CA-mutated tumors were found to be more likely to be ER-α positive (P &amp;lt; 0.05) and pAKT positive (P &amp;lt; 0.05). There was no significant association between PIK3CA mutations and p53 mutation status. PIK3CA mutations were significantly (P &amp;lt; 0.05) associated with a favorable prognosis, and multivariate analysis showed that PIK3CA mutation status was a significant (P &amp;lt; 0.05) prognostic factor independent of the other conventional prognostic factors. Conclusions: The frequency of PIK3CA mutations in Japanese breast cancers is similar to that of Caucasian breast cancers. Association of PIK3CA mutations with positive pAKT and positive ER-α suggests that PIK3CA mutations might exert their effects through activation of the phosphatidylinositol 3-kinase/AKT/ER-α pathway. PIK3CA mutations seem to have a potential to be used as an indicator of favorable prognosis.
POEMS syndrome: 2014 Update on diagnosis, risk‐stratification, and management
Authors: Angela Dispenzieri
Journal: American Journal of Hematology (2014)

Disease overview : POEMS syndrome is a paraneoplastic syndrome due to an underlying plasma cell neoplasm. The major criteria for the syndrome are polyradiculoneuropathy, clonal plasma cell disorder (PCD), sclerotic bone lesions, elevated vascular endothelial growth factor, and the presence of Castleman disease. Minor features include organomegaly, endocrinopathy, characteristic skin changes, papilledema, extravascular volume overload, and thrombocytosis. Diagnoses are often delayed because the syndrome is rare and can be mistaken for other neurologic disorders, most commonly chronic inflammatory demyelinating polyradiculoneuropathy. POEMS syndrome should be distinguished from the Castleman disease variant of POEMS syndrome, which has no clonal PCD and typically little to no peripheral neuropathy but has several of the minor diagnostic criteria for POEMS syndrome. Diagnosis : The diagnosis of POEMS syndrome is made with three of the major criteria, two of which must include polyradiculoneuropathy and clonal PCD, and at least one of the minor criteria. Risk stratification : Because the pathogenesis of the syndrome is not well understood, risk stratification is limited to clinical phenotype rather than specific molecular markers. The number of clinical criteria is not prognostic, but the extent of the PCD is. Those patients with an iliac crest bone marrow biopsy that does not reveal a plasma cell clone are candidates for local radiation therapy; those with a more extensive or disseminated clone will be candidates for systemic therapy. Risk‐adapted therapy : For those patients with a dominant sclerotic plasmacytoma, first line therapy is irradiation. Patients with diffuse sclerotic lesions or disseminated bone marrow involvement and for those who have progression of their disease 3–6 months after completing radiation therapy should receive systemic therapy. Corticosteroids are temporizing, but alkylators are the mainstay of treatment, either in the form of low dose conventional therapy or high dose with stem cell transplantation. The benefit of anti‐VEGF antibodies is conflicting. Lenalidomide shows promise with manageable toxicity. Thalidomide and bortezomib also have activity, but their benefit needs to be weighed against their risk of exacerbating the peripheral neuropathy. Prompt recognition and institution of both supportive care measures and therapy directed against the plasma cell result in the best outcomes. Am. J. Hematol. 89:214–223, 2014. © 2014 Wiley Periodicals, Inc.
Congenital dislocation of the hip.
Journal: BMJ (1977)

then we need to know that the advice given is sound and that it is effective in changing attitudes, in reducing delay in diagnosis, and-ultimately-in reducing mortality, and especially mortality in youth and middle age.The Cancer Research Campaign has recently allocated some of its funds to support research projects concerned with cancer education, so that finance is available for evaluation.Short of money, the NHS needs to make the best use of existing knowledge; and prevention offers the best hope of reducing both the toll of cancer and the demands it makes on resources.
Glutathione S-transferase M1 polymorphism: a risk factor for hepatic venoocclusive disease in bone marrow transplantation
Authors: Alok Srivastava, Balasubramanian Poonkuzhali, Ramachandran V. Shaji, Biju George, Vikram Mathews, Mammen Chandy, Rajagopal Krishnamoorthy
Journal: Blood (2004)
Prevention of Ventilator-associated Pneumonia by Oral Decontamination
Authors: DENNIS C. J. J. BERGMANS, MARC J. M. BONTEN, CARLO A. GAILLARD, JOHAN C. PALING, SIEBE van der GEEST, FRANK H. van TIEL, ANTON J. BEYSENS, PETER W. de LEEUW, ELLEN E. STOBBERINGH
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

Colonization of the intestinal tract has been assumed to be important in the pathogenesis of ventilator-associated pneumonia (VAP), but relative impacts of oropharyngeal, gastric, or intestinal colonization have not been elucidated. Our aim was to prevent VAP by modulation of oropharyngeal colonization, without influencing gastric and intestinal colonization and without systemic prophylaxis. In a prospective, randomized, placebo-controlled, double-blind study, 87 patients received topical antimicrobial prophylaxis (gentamicin/ colistin/vancomycin 2% in Orabase, every 6 h) in the oropharynx and 139 patients, divided over two control groups, received placebo (78 patients were studied in the presence of patients receiving topical prophylaxis [control group A] and 61 patients were studied in an intensive care unit where no topical prophylaxis was used [control group B]). Baseline characteristics were comparable in all three groups. Topical prophylaxis eradicated colonization present on admission in oropharynx (75% in study group versus 0% in control group A [p < 0.00001] and 9% in control group B patients [p < 0.00001]) and in trachea (52% versus 22% in A [p = 0.03] and 7% in B [p = 0.004]). Moreover, topical prophylaxis prevented acquired oropharyngeal colonization (10% versus 59% in A [p < 0.00001] and 63% in B [p < 0.00001]). Colonization rates in stomach and intestine were not affected. Incidences of VAP were 10% in study patients, 31% in Group A, and 23% in Group B patients (p = 0.001 and p = 0.04, respectively). This was not associated with shorter durations of ventilation or ICU stay or better survival. Oropharyngeal colonization is of paramount importance in the pathogenesis of VAP, and a targeted approach to prevent colonization at this site is a very effective method of infection prevention.Keywords: cross infection, prevention and control; respiration, artificial, adverse effects; antibiotics, administration and dosage infection control methods; pneumonia, etiology, prevention and control; intubation, intratracheal, adverse effects
Combination of nivolumab (nivo) + ipilimumab (ipi) in the treatment of patients (pts) with deficient DNA mismatch repair (dMMR)/high microsatellite instability (MSI-H) metastatic colorectal cancer (mCRC): CheckMate 142 study.
Authors: Thierry Andre, Sara Lonardi, Ka Yeung Mark Wong, Michael Morse, Raymond S. McDermott, Andrew Graham Hill, Alain Hendlisz, Heinz-Josef Lenz, Joseph W. Leach, Rebecca Anne Moss, Z. Alexander Cao, Jean-Marie Ledeine, Emily Chan, Scott Kopetz, Michael J. Overman
Journal: Journal of Clinical Oncology (2017)

3531 Background: Nivo, a fully human anti-PD-1 mAb, provided an ORR of 31%, durable responses (median DOR not reached), and a 12-mo OS rate of 73.8% in pts with dMMR/MSI-H mCRC (Overman M, et al. 2017). Preliminary analysis of nivo + ipi, a humanized anti-CTLA-4 mAb, demonstrated manageable safety and promising efficacy in pts with dMMR/MSI-H mCRC (Overman M, et al . 2016). Here we report interim safety and efficacy of nivo + ipi in this pt population from the Checkmate 142 study (NCT02060188). Methods: Pts with dMMR/MSI-H mCRC who progressed on or were intolerant of ≥1 prior line of therapy received nivo 3 mg/kg + ipi 1 mg/kg q3w × 4 doses followed by nivo 3 mg/kg q2w until discontinuation due to disease progression or other reason. Primary endpoint was investigator-reported ORR by RECIST 1.1. Other endpoints included DOR, PFS, OS, safety, and tolerability. Results: 27 pts with dMMR/MSI-H mCRC treated with nivo + ipi received the first dose ≥6 mo prior to the database lock (DBL; Sept 2016). Of these pts, 93% received ≥2 prior lines of therapy. At the time of DBL, 44% of pts remained on treatment, and 14 pts had discontinued therapy due to disease progression (n=8) or TRAEs (n=6). ORR was 41% and disease control rate (DCR) was 78% (Table). The median time to response was 2.7 mo, and 82% of responses (9/11) were ongoing at 6 mo. The medians for DOR, PFS and OS had not been reached. Grade 3–4 TRAEs occurred in 10 pts (37%).TRAEs leading to discontinuation included acute kidney injury, increased transaminases, necrotizing myositis, sarcoidosis, dyspnea, and thrombocytopenia (1 each). No deaths were attributed to therapy. Conclusions: Initial analysis ofnivo + ipi in pts with ≥6-mo follow-up demonstrated a manageable safety profile and clinical activity characterized by a high DCR and encouraging survival benefit. This study is ongoing, and updated efficacy and biomarker analyses of ≈80 pts with ≥6-mo follow-up will be presented. Clinical trial information: NCT02060188. [Table: see text]
Revised Recommendations of the International Working Group for Diagnosis, Standardization of Response Criteria, Treatment Outcomes, and Reporting Standards for Therapeutic Trials in Acute Myeloid Leukemia
Authors: Bruce D. Cheson, John M. Bennett, Kenneth J. Kopecky, Thomas Büchner, Cheryl L. Willman, Elihu H. Estey, Charles A. Schiffer, Hartmut Doehner, Martin S. Tallman, T. Andrew Lister, Francesco Lo-Coco, Roel Willemze, Andrea Biondi, Wolfgang Hiddemann, Richard A. Larson, Bob Löwenberg, Miguel A. Sanz, David R. Head, Ryuzo Ohno, Clara D. Bloomfield
Journal: Journal of Clinical Oncology (2003)

An International Working Group met to revise the diagnostic and response criteria for acute myelogenous leukemia originally published in 1990, as well as to provide definitions of outcomes and reporting standards to improve interpretability of data and comparisons among trials. Since the original publication, there have been major advances in our understanding of the biology and molecular genetics of acute leukemia that are clinically relevant and warrant incorporation into response definitions. Differences from the 1990 recommendations included a category of leukemia-free state, new criteria for complete remission, including cytogenetic and molecular remissions and remission duration. Storage of viable blasts for correlative studies is important for future progress in the therapy of these disorders.
Lumbar Spinal Stenosis
Authors: STEPHEN HALL
Journal: Annals of Internal Medicine (1985)

Our experience with 68 patients with strictly defined, myelographically proven, surgically confirmed lumbar spinal stenosis seen over a 30-month period was reviewed. Pseudoclaudication was the commonest symptom (94%) and was described by patients as pain (93%), numbness (63%), or weakness (43%). Symptoms were frequently bilateral (68%) and generally relieved by flexing the lumbosacral spine. Neurologic abnormalities were found in a minority of patients and were usually mild. Electromyography showed one or more lumbosacral radiculopathies in 34 of 37 patients examined. Radiographic evidence of degenerative disk or joint disease was found in 63 patients. All patients had stenosis on myelography, with narrowing at L2, L3, and L4 being the commonest; 30% had multi-level stenosis. Two of ten computed tomograms were normal. Surgery was extensive; 72% of patients had three or more laminae removed. At a mean of 4 years after surgery, 84% of patients reported that surgery had yielded good to excellent results.
Chronic Kidney Disease in Older People
Authors: Andrew S. Levey, Lesley A. Inker, Josef Coresh
Journal: JAMA (2015)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
The Length of the Cervix and the Risk of Spontaneous Premature Delivery
Authors: Jay D. Iams, Robert L. Goldenberg, Paul J. Meis, Brian M. Mercer, Atef Moawad, Anita Das, Elizabeth Thom, Donald McNellis, Rachel L. Copper, Francee Johnson, James M. Roberts
Journal: New England Journal of Medicine (1996)

The role of the cervix in the pathogenesis of premature delivery is controversial. In a prospective, multicenter study of pregnant women, we used vaginal ultrasonography to measure the length of the cervix; we also documented the incidence of spontaneous delivery before 35 weeks' gestation.
Tumor Necrosis Factor Inhibitors for Inflammatory Bowel Disease
Authors: Ole Haagen Nielsen, Mark Andrew Ainsworth
Journal: New England Journal of Medicine (2013)

A 35-year-old man presents with an exacerbation of Crohn's disease. Treatment with a TNF inhibitor is recommended. TNF inhibitors block the effects of the proinflammatory cytokine TNF-α, and several have been shown to be effective in treating inflammatory bowel disease.
Survival, response duration, and activity by BRAF mutation (MT) status of nivolumab (NIVO, anti-PD-1, BMS-936558, ONO-4538) and ipilimumab (IPI) concurrent therapy in advanced melanoma (MEL).
Authors: Mario Sznol, Harriet M. Kluger, Margaret K. Callahan, Michael Andrew Postow, Ruth Ann Gordon, Neil Howard Segal, Naiyer A. Rizvi, Alexander M. Lesokhin, Michael B. Atkins, John M. Kirkwood, Matthew M. Burke, Amanda L. Ralabate, Angel L. Rivera, Stephanie Anne Kronenberg, Blessing Agunwamba, William Feely, Quan Hong, Suba Krishnan, Ashok Kumar Gupta, Jedd D. Wolchok
Journal: Journal of Clinical Oncology (2014)

LBA9003^ Background: We report updated survival and clinical activity in initially enrolled cohorts and activity by BRAF MT status in a phase I trial of concurrent and sequenced NIVO + IPI. Methods: MEL pts (n=53, enrolled 2009-2012, data analysis Dec 2013) with ≤3 prior therapies received IV concurrent NIVO + IPI, Q3Wk × 4 doses, followed by NIVO Q3Wk × 4. At wk 24, NIVO + IPI continued Q12Wk × 8 in pts with disease control and no DLT. Tumor responses were evaluated by WHO and immune-related criteria. Results: Pt characteristics included stage M1c: 55% and prior systemic therapy: 40%. Across doses, 1- and 2-y OS rates were 82% and 75%. Clinical activity was similar to previous reports except CRs rose to 9/53 (17%). Pts with/without tumor BRAF MT (n=36) had similar activity (Table). By wk 36, 42% demonstrated ≥80% tumor reduction. Median duration of response (DOR) was not reached (NR). Of 22 pts with objective response, 14 (64%) had DOR ≥24 wk (range: 25+, 106+). Treatment-related adverse events were as reported previously: grade 3-4, 53% of pts; most common: ↑ lipase and AST (13% ea). Data for sequenced cohorts are shown (Table). Conclusions: Concurrent NIVO + IPI therapy showed encouraging survival and a manageable safety profile in advanced MEL pts. Responses were observed regardless of BRAF MT status and were durable in the majority of pts. Forty additional pts were enrolled (last pt: Nov 2013) on a cohort of NIVO 1 mg/kg + IPI 3 mg/kg Q3Wk × 4 doses, followed by NIVO 3mg/kg Q2Wk (the selected regimen for phase II/III trials). Clinical trial information: NCT01024231. [Table: see text]
The impact of chronic urticaria on the quality of life
Authors: B.F. O'DONNELL, F. LAWLOR, J. SIMPSON, M. MORGAN, M.W. GREAVES
Journal: British Journal of Dermatology (1997)

The impact of chronic urticaria (CU) on the quality of life is undocumented. We assessed quality of life in patients with CU, including patients with associated delayed pressure urticaria (DPU). One hundred and forty–two out–patients completed self–administered questionnaires: a disease–specific, purpose designed questionnaire, and the Nottingham health profile (NHP). Many patients reported problems attributable to their skin condition in facets of everyday life including home management, personal care, recreation and social interaction, mobility, emotional factors, sleep, rest and work. The NHP part I scores showed restriction in the areas of mobility, sleep, energy, and demonstrated pain, social isolation and altered emotional reactions. Part II of the NHP showed that patients experienced difficulties in relation to work, looking after the home, social life, home relationships, sex life, hobbies and holidays. The patients with DPU had significantly more problems with mobility, gardening and choice of clothing than the uncomplicated CU patients. They also suffered more pain, had more problems with work and were more restricted in their hobbies.
Assessment of fludarabine plus cyclophosphamide for patients with chronic lymphocytic leukaemia (the LRF CLL4 Trial): a randomised controlled trial
Authors: D Catovsky, S Richards, E Matutes, D Oscier, MJS Dyer, RF Bezares, AR Pettitt, T Hamblin, DW Milligan, JA Child, MS Hamilton, CE Dearden, AG Smith, AG Bosanquet, Z Davis, V Brito-Babapulle, M Else, R Wade, P Hillmen
Journal: The Lancet (2007)
Readmissions After Revascularization Procedures for Peripheral Arterial Disease
Authors: Eric A. Secemsky, Marc Schermerhorn, Brett J. Carroll, Kevin F. Kennedy, Changyu Shen, Linda R. Valsdottir, Bruce Landon, Robert W. Yeh
Journal: Annals of Internal Medicine (2017)

Background: Limited data suggest high rates of unplanned rehospitalization after endovascular and surgical revascularization for peripheral arterial disease. However, the overall burden of readmissions has not been comprehensively explored. Objective: To evaluate nationwide readmissions after peripheral arterial revascularization for peripheral arterial disease and to assess whether readmission risk varies among hospitals. Design: Retrospective cohort study. Setting: 1085 U.S. acute care hospitals participating in the Nationwide Readmissions Database. Patients: 61 969 unweighted hospitalizations of patients with peripheral arterial disease who had peripheral arterial revascularization and were discharged alive between 1 January and 30 November 2014. Measurements: 30-day readmission rates, causes, and costs of unplanned rehospitalizations after peripheral arterial revascularization; 30-day risk-standardized readmission rates (RSRRs), calculated using hierarchical logistic regression, to assess for heterogeneity of readmission risk between hospitals. Results: Among 61 969 hospitalizations of patients with peripheral arterial disease who were discharged alive after peripheral arterial revascularization, the 30-day nonelective readmission rate was 17.6%. The most common cause of readmission was procedural complications (28.0%), followed by sepsis (8.3%) and complications due to diabetes mellitus (7.5%). Among rehospitalized patients, 21.0% underwent a subsequent peripheral arterial revascularization or lower extremity amputation, 4.6% died, and the median cost of a readmission was $11 013. Thirty-day RSRRs varied from 10.0% to 27.3% (interquartile range, 16.6% to 18.8%). Limitation: Inability to distinguish out-of-hospital deaths after discharge and potential misclassification bias due to use of billing codes to ascertain diagnoses and interventions. Conclusion: More than 1 in 6 patients with peripheral arterial disease who undergo peripheral arterial revascularization have unplanned readmission within 30 days, with high associated mortality risks and costs. Procedure- and patient-related factors were the primary reasons for readmission. Readmission rates varied moderately between institutions after hospital case mix was accounted for, suggesting that differences in hospital quality may only partially account for readmission. Primary Funding Source: Smith Center for Outcomes Research in Cardiology, Beth Israel Deaconess Medical Center.
The Rule of Double Effect — A Critique of Its Role in End-of-Life Decision Making
Authors: Timothy E. Quill, Rebecca Dresser, Dan W. Brock
Journal: New England Journal of Medicine (1997)

According to the ethical principle known as the "rule of double effect," effects that would be morally wrong if caused intentionally are permissible if foreseen but unintended. This principle is often cited to explain why certain forms of care at the end of life that result in death are morally permissible and others are not.19 According to the rule, administering high-dose opioids to treat a terminally ill patient's pain may be acceptable even if the medication causes the patient's death. In contrast, the rule does not authorize practices such as physician-assisted suicide, voluntary euthanasia, and certain instances of forgoing . . .